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利福平对异烟肼在小鼠原代肝细胞内代谢的影响
引用本文:蔡大伟,侯艳宁,鲁传冬,李亚楠,薛改.利福平对异烟肼在小鼠原代肝细胞内代谢的影响[J].解放军药学学报,2009,25(5):414-416.
作者姓名:蔡大伟  侯艳宁  鲁传冬  李亚楠  薛改
作者单位:1. 解放军第251医院,河北,张家口,075000
2. 白求恩国际和平医院,河北,石家庄,050082
摘    要:目的探讨异烟肼(INH)与利福平(RFP)合用致肝毒性增加的部分作用机理。方法采用在体心脏灌流法获取小鼠原代肝细胞,将其常规培养5d后,分别用含INH(87.5μmol.L^-1)和INH+RFP(87.5μmol.L^-1+48.6μmol.L^-1)培养液培养48h,液相色谱-电喷雾质谱联用法测定2组培养液中INH及其代谢产物乙酰肼(Acetylhydrazine,AHZ)和肼(Hydrazine,HZ)的浓度。结果与INH组比较,INH+RFP组AHZ和HZ浓度增加,有显著性差异(P〈0.01)。结论RFP和INH合用后使INH肝毒性代谢物浓度增加,可能是其肝毒性增加的原因之一。

关 键 词:异烟肼  利福平  代谢

The Effect of Rifampicin on the Metabolism of Isoniazid
CAI Da-Wei,HOU Yan-Ning,LU Chuan-Dong,LI Ya-Nan,XUE Gai.The Effect of Rifampicin on the Metabolism of Isoniazid[J].Pharmaceutical Journal of Chinese People's Liberation Army,2009,25(5):414-416.
Authors:CAI Da-Wei  HOU Yan-Ning  LU Chuan-Dong  LI Ya-Nan  XUE Gai
Institution:1.Hospital 251 of PLA,Zhangjiakou 075000,Hebei China;2.Bethune International Peace Hospital, Shijiazhuang 050082, Hebei China)
Abstract:Aim To investigate the mechanism of isoniazid (INH)and rifampicin(RFP). Methods Mouse hepatocytes were obtained through cardio-perfusion in mice and isolated by two-step in situ collagenase perfusion methods, after five days of culture of mouse hepatocytes, the culture hquid was replaced by INH(87.5μmol.L^-1 ) , INH + RFP(87.5μmol.L^-1 +48.6μmol.L^-1 ). the concentration of AHZ and HZ was determined by LC/ESI-MS in 48h. Results The concentration of AHZ and HZ increased more in the INH + RFP group than in the INH group( P 〈 0.01 ). Conclusion RFP can increase the concentration of acetylhydrazine (AHZ) and ( hydrazine ) HZ, which may increase the hepatotoxicity of INH.
Keywords:isoniazid  rifampicin  metabolism
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